Patients with a primary invasive melanoma are recommended to undergo excision of the primary
lesion with a wide margin. There is evidence that less radical margins of excision may be
just as safe. This is a randomised controlled trial of 1 cm versus 2 cm margin of excision of
the primary lesion for adult patients with stage II primary invasive cutaneous melanomas
(AJCC 8th edition) to determine differences in disease-free survival. A reduction in margins
is expected to improve patient quality of life.

This study will determine whether there is a difference in disease-free survival rates for
patients with primary cutaneous melanoma with Breslow thickness > 2mm or 1-2mm with
ulceration (pT2b-pT4b, AJCC 8th edition), treated with either a 1cm excision margin or 2cm
margin. The study is designed to be able to prove or disprove that there is no difference in
risk of the tumour recurring around the scar or anywhere else in the body between the two
groups of patients. If the study shows no risk of tumour recurrence then we will also be able
to determine how much of an impact the narrower excision has on patients in terms of improved
quality of life and reduced side effects from the surgery and melanoma disease. This trial
will also evaluate and determine the economic impact of narrower excision margins on the
health services and society in general.

Inclusion Criteria:

1. Patients must have a stage II primary invasive cutaneous melanoma with Breslow
thickness >2mm without ulceration), or >1mm (with ulceration only) (pT2b-pT4b, AJCC
8th edition) as determined by diagnostic biopsy (narrow excision, incision or punch
biopsy) and subsequent histopathological analysis.

2. Must have a primary melanoma that is cutaneous (including head, neck, trunk,
extremity, scalp, palm or sole).

3. An uninterrupted 2cm margin must be technically feasible around biopsy scar or primary
melanoma.

4. Surgery (which refers to the staging sentinel node biopsy and wide local excision as
these are both to be done on the same day) must be completed within 120 days of the
original diagnosis.

5. Patients must be 18 years or older at time of consent.

6. Patient must be able to give informed consent and comply with the treatment protocol
and follow-up plan.

7. Life expectancy of at least 5 years from the time of diagnosis, not considering the
melanoma in question, as determined by the PI.

8. Patients must have an ECOG performance score between 0 and 1.

9. A survivor of prior cancer is eligible provided that ALL of the following criteria are
met and documented:

- The patient has undergone potentially curative therapy for all prior
malignancies,

- There has been no evidence of recurrence of any prior malignancies for at least
FIVE years (except for successfully treated cervical or non-melanoma skin cancer
with no evidence of recurrence), and

- The patient is deemed by their treating physician to be at low risk of recurrence
from previous malignancies.

Exclusion Criteria:

Patients will be excluded from the study for ANY of the following reasons:

1. Uncertain diagnosis of melanoma i.e. so-called 'melanocytic lesion of unknown
malignant potential'.

2. Patient has already undergone wide local excision at the site of the primary index
lesion.

3. Patient unable or ineligible to undergo staging sentinel lymph node biopsy of the
primary index lesion.

4. Desmoplastic or neurotropic melanoma: with any patient where pathology determines
melanoma as PURE desmoplastic (as per WHO definition of >90% desmoplasia), they are
not eligible for this study. However other desmoplasia or mixed subtypes are eligible
unless there is neurotropism present (peri-neural invasion).Peri-neural invasion does
not include entrapment of nerves within the main primary tumour mass.
Microsatellitosis as per AJCC 8th edition definition

5. Subungual melanoma

6. Patient has already undergone a local flap reconstruction of the defect after excision
of the primary and determination of an accurate excision margin is impossible.

7. History of previous or concurrent (i.e., second primary) invasive melanoma.

8. Melanoma located distal to the metacarpophalangeal joint; on the tip of the nose; the
eyelids or on the ear; genitalia, perineum or anus; mucous membranes or internal
viscera.

9. Physical, clinical, radiographic or pathologic evidence of satellite, in-transit,
regional, or distant metastatic melanoma.

10. Patient has undergone surgery on a separate occasion to clear the lymph nodes of the
probable draining lymphatic field, including sentinel lymph node biopsy, of the index
melanoma.

11. Any additional solid tumour or hematologic malignancy during the past 5 years except
T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine/cervical
cancer.

12. Melanoma-related operative procedures not corresponding to criteria described in the
protocol.

13. Planned adjuvant radiotherapy to the primary melanoma site after Wide Local Excision
is not permitted as part of the protocol and any patients given this treatment would
be excluded from the study.

14. History of organ transplantation.

15. Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at
enrolment or within 6 months prior to enrolment.

Pregnancy is not a specific exclusion criterion for this trial, though it may not be
clinically appropriate to perform a wide excision and sentinel node biopsy until the
pregnancy has been completed, which is likely to exclude the patient due to violation of
inclusion criterion 4. We would advise careful counselling of the patient prior to
enrolling the patient, which would include a discussion at the treating centre's
multidisciplinary team meeting or tumour board. We would strongly advise contacting the
central trial office to discuss the case prior to enrolling on the study.

If you are interested in participating in this study, call The JamesLine at 800-293-5066 to make an appointment with the principal investigator listed or ask your doctor if you are eligible for this study.